Electrification of remote zones is often characterized by high energy costs as a result of the fossil fuels supply and cost associated to its logistic. This study performs a theoretical model and optimization of an ocean thermal energy conversion (OTEC) system coupled to an organic Rankine cycle (ORC) generator for small scale applications in the San Blas archipelago (Panama). The gross electric power has been previously set at 125 kW for the eleven working fluids selected: ammonia, R152a, R1234yf, R1234ze, R125, R134a, R161, propane, isobutene, RE143a and decafluorobutane. Results show R1234yf gets the maximum thermodynamic and net electric efficiency (3.60% and 2.57%, respectively). Ammonia reaches the maximum net electric power (99.3 kW) and, thus, the lowest pumping losses (20.59% of the gross). Besides, despite decafluorobutane shows slightly lower electric power (98 kW) and efficiencies, this fluid does not present environmental hazardous features. Sensitivity analyses show that all performance parameters of the plant are strongly affected by deep and surface seawater temperature variation. Finally, for a surface seawater temperature of 30 °C and deep 5 °C, the net electric power reached is 94.6 kW for R1234yf, 99.3 kW for ammonia and 98.0 kW for decafluorobutane. The net electric efficiency is 2.57%, 2.53% and 2.42%, and the total area required by the heat exchangers is 890 m2, 940 m2 and 986 m2, respectively.